Balloon catheters having a plurality of needles for the injection of one or more therapeutic agents

ABSTRACT

There are disclosed apparatus and methods for treating tissue by delivering at least one therapeutic agent into the tissue. In one embodiment, the apparatus comprises a catheter and a balloon member disposed on a distal region of the catheter. A plurality of pockets are disposed on the balloon member, and a plurality of needles are associated with each of the plurality of pockets. The plurality of needles are configured to engage tissue when the balloon is in the inflated state, and further are configured to disperse a therapeutic agent from an associated pocket into the tissue when the balloon is in the inflated state. A first needle of the plurality of needles may comprise a length that is different than a second needle, permitting the delivery of first and second therapeutic agents to different depths within the tissue.

RELATED APPLICATIONS

The present patent document is a divisional application that claims thebenefit of priority under 35 U.S.C. §121 of U.S. patent application Ser.No. 13/059,856 filed Mar. 23, 2011, which is a §371 filing based on PCTApplication Serial No. PCT/US2009/004811, filed Aug. 24, 2009 (andpublished as WO 2010/024871A1 on Mar. 4, 2010), designating the UnitedStates and published in English, which claims the benefit of the filingdate under 35 U.S.C. §119(e) of Provisional U.S. Patent Application Ser.No. 61/091,894, filed Aug. 26, 2008. All of the foregoing applicationsare hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to apparatus for treating tissue at atarget site, and to a method of treating tissue at a target site. Thepreferred embodiment relates to a balloon catheter provided with aplurality of needles configured to deliver one or more therapeuticagents into the tissue.

BACKGROUND ART

There are several instances in which it may become desirable tointroduce therapeutic agents into a human or animal body. For example,therapeutic drugs or bioactive materials may be introduced to achieve abiological effect. The biological effect may include an array oftargeted results, such as inducing hemostasis, reducing restenosislikelihood, or treating cancerous tumors or other diseases.

Many of such therapeutic agents are injected using an intravenous (IV)technique and via oral medicine. While such techniques permit thegeneral introduction of medicine, in many instances it may be desirableto provide localized or targeted delivery of therapeutic agents, whichmay allow for the guided and precise delivery of agents to selectedtarget sites.

For example, localized delivery of therapeutic agents to a tumor mayreduce the exposure of the therapeutic agents to normal, healthytissues, which may reduce potentially harmful side effects. Similarly,therapeutic agents may be delivered locally to a diseased portion of acoronary vessel to reduce, halt or reverse the progression of astenosis, or may be delivered to a diseased portion of the aorta inorder to reduce, halt or reverse the progression of an abdominal aorticaneurysm.

Localized delivery of therapeutic agents has been performed usingcatheters and similar introducer devices. By way of example, a cathetermay be advanced towards a target site within the patient, then thetherapeutic agent may be injected through a lumen of the catheter to thetarget site. Typically, a syringe or similar device may be used toinject the therapeutic agent into the lumen of the catheter. Thetherapeutic agent then may exit through a port disposed in a lateralsurface at the distal end of the catheter.

Typical catheter systems that locally deliver a therapeutic agent arelimited in that they may only deliver one therapeutic agent at a timeinto the tissue. Moreover, it may be difficult to deliver a therapeuticagent to different depths into the tissue, resulting in treatment ofonly a portion of the tissue, e.g., the intimal layer, with one type oftherapeutic agent. If multiple therapeutic agents are desired, or one ormore agents are intended to be delivered at different tissue depths,then multiple components may need to be sequentially removed andinserted to achieve this result.

DISCLOSURE OF THE INVENTION

The present invention seeks to provide improved treatment of tissue at atarget site.

According to an aspect of the present invention, there is provided anapparatus for treating tissue of a target site as specified in claim 1.

According to another aspect of the present invention, there is providedan apparatus for treating tissue at a target site as specified in claim9.

According to another aspect of the present invention, there is provideda method of treating tissue at a target site as specified in claim 15.

The present invention provides apparatus and methods for treating tissueby delivering at least one therapeutic agent into the tissue. In a firstembodiment, the apparatus comprises an inner cannula and an outercannula disposed substantially co-axially over the inner cannula to forma delivery channel therebetween. An inner balloon member is disposed ona distal region of the inner cannula, and an outer balloon member isdisposed substantially over the inner balloon member. A plurality ofpockets are disposed on the outer balloon member, or formed integrallywith the balloon, and at least one needle is associated with at leastone of the plurality of pockets. The inner balloon member is inflated tocause the plurality of needles to engage tissue, and a therapeutic agentis delivered through the plurality of needles, via the delivery channeland the plurality of pockets, to dispense the therapeutic agent into thetissue.

In another embodiment, the apparatus comprises a catheter, a balloonmember, and a plurality of pockets disposed on the balloon member. Aplurality of needles, associated with each of the plurality of pockets,are configured to engage tissue when the balloon is in the inflatedstate, and are further configured to disperse a therapeutic agent froman associated pocket into the tissue when the balloon is in the inflatedstate. A first needle may comprise a length that is different than alength of a second needle, thereby permitting the delivery of first andsecond therapeutic agents to different depths within the tissue.

In one embodiment, each of the plurality of pockets may be separate anddiscrete from another pocket, and a therapeutic agent is disposedindividually within each of the plurality of pockets. Alternatively,each of the plurality of pockets may be placed in fluid communicationwith at least one other pocket. In the latter embodiment, a first seriesof pockets comprising needles having first lengths may be placed influid communication with one another, and a second series of pocketscomprising needles having second lengths may be placed in fluidcommunication with one another. This allows a first therapeutic agent tobe delivered through the first series of pockets to a first tissuedepth, and a second therapeutic agent to be delivered through the secondseries of pockets to a second tissue depth.

Advantageously, one or more therapeutic agents may be locally deliveredto a desired target site in a fast and efficient manner. Moreover, ifmultiple therapeutic agents are desired, different therapeutic agentsmay be delivered to different tissue locations and depths, without theneed to remove and insert multiple different components.

Other systems, methods, features and advantages of the invention willbe, or will become, apparent to one with skill in the art uponexamination of the following figures and detailed description. It isintended that all such additional systems, methods, features andadvantages be within the scope of the invention, and be encompassed bythe following claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention are described below, by way ofexample only, with reference to the accompanying drawings in which:

FIG. 1 is a side view of an apparatus for delivering at least onetherapeutic agent according to a first embodiment;

FIG. 2 is an enlarged side-sectional view of a portion of the apparatusof FIG. 1 engaging tissue;

FIGS. 3-5 are side-sectional views illustrating an exemplary sequence ofdeployment of a pocket and an associated needle;

FIG. 6 is a side view of another embodiment of apparatus for deliveringat least one therapeutic agent;

FIG. 7 is a cross-sectional view along line A-A of FIG. 6;

FIG. 8 is a side view of another embodiment of apparatus for deliveringat least one therapeutic agent;

FIG. 9 is a cross-sectional view along line B-B of FIG. 8;

FIG. 10 is a perspective view of an exemplary proximal assembly that maybe used in conjunction with the apparatus of FIG. 8;

FIG. 11 is a schematic view of an exemplary arrangement of multiplepockets and needles;

FIG. 12 is a perspective view of another embodiment of apparatus fordelivering at least one therapeutic agent; and

FIG. 13 is a side view of another embodiment of apparatus for deliveringat least one therapeutic agent.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the present application, the term “proximal” refers to a directionthat is generally toward a physician during a medical procedure, whilethe term “distal” refers to a direction that is generally toward atarget site within a patient's anatomy during a medical procedure.

Referring now to FIGS. 1-2, a first embodiment of an apparatus fordelivering at least one therapeutic agent to treat a medical condition,such as a stenosis or an aneurysm, is described. The apparatus 20comprises an inner cannula 30 and an outer cannula 40, each havingproximal and distal regions. The inner cannula 30 has an inflation lumen32 formed therein, as shown in FIG. 1. The outer cannula 40 issubstantially co-axially disposed around the inner cannula 30, therebyforming a delivery channel 42 that may comprise an annular shape.

The inner cannula 30 and the outer cannula 40 may comprise a flexible,tubular member that may be formed from one or more semi-rigid polymers.For example, the inner and outer cannulas 30 and 40 may be manufacturedfrom polyurethane, polyethylene, tetrafluoroethylene,polytetrafluoroethylene, fluorinated ethylene propylene, nylon, PEBAX orthe like. In the embodiment of FIGS. 1-2, while two separate inner andouter cannulas 30 and 40 are shown, it will be apparent that oneintegrally-formed catheter having multiple lumens may be employed, e.g.,as shown in FIGS. 8-10 below, or alternatively, greater than twocannulas may be employed as part of a catheter assembly.

The apparatus 20 also includes an inner balloon member 50 and an outerballoon member 60 disposed substantially over the inner balloon member50. The inner balloon member 50 has an inner surface 55 and an outersurface 56, and may be configured in a manner similar to a conventionalinterventional balloon, such as an angioplasty balloon. A proximal endof the inner balloon member 50 may be coupled to an outer surface of theinner cannula 30 at a proximal affixation point 58, while a distal endof the inner balloon member 50 may be coupled to an outer surface of theinner cannula 30 at a distal affixation point 59, as shown in FIG. 1.The inner balloon member 50 may be attached at these locations using anysuitable adhesive, such as a biocompatible glue, and/or usingheat-shrink tubing, heat bonding, laser bonding, welding, solventbonding, one or more tie-down bands, or the like. Optionally, one ormore proximal and distal radiopaque markers 72 and 74 may be provided inthe vicinity of the proximal and distal affixation points 58 and 59,respectively.

At least one port 54 may be formed in the inner cannula 30 to providefluid communication between the inflation lumen 32 of the inner cannula30 and an interior space 57 of the inner balloon member 50. A proximalregion of the inflation lumen 32 may be coupled to an inflation source.The provision of a fluid, such as saline, through the inflation lumen 32causes inflation of the inner balloon member 50 to the inflated state,as shown in FIG. 1.

The outer balloon member 60 has a proximal end that is coupled to adistal end of the outer cannula 40 at a proximal affixation point 68,and the outer balloon member 60 also includes a distal end that iscoupled to the inner cannula 30 at a distal affixation point 69, asshown in FIG. 1. The outer balloon member 60 also includes at least onepocket 64 having a needle 80 associated therewith for delivering atherapeutic agent. Preferably, multiple pockets 64 and associatedneedles 80 are provided, as shown in FIG. 1.

The plurality of pockets 64 and needles 80 may be disposed at multiplelocations around the perimeter of the outer balloon member 60, and maybe placed in fluid communication with the delivery channel 42, as shownin FIG. 1. As explained in further detail below, when one or moretherapeutic agents are delivered through the annular space between theinner and outer cannulas 30 and 40, the therapeutic agents may bedelivered into tissue via the plurality of needles 80.

The inner and outer balloon members 50 and 60 may be manufactured from amaterial including, but not limited to, PEBAX, nylon, Hytrel, Arnitel orother polymers, which may be suitable for use during an interventionalprocedure. Each of the pockets 64 may be integrally or externallycoupled to an exterior surface of the outer balloon member 60. Forexample, the pockets 64 may be integrally formed into the outer balloonmember 60 by molding the pockets 64 into a desired shape, e.g., abulbous, circular, square, rectangular, oval, hexagonal or octagonalshape, or any other design.

The needles 80 may comprise a suitable material and shape configured topierce through a target site, such as tissue of a vessel wall or duct, astenosis, and the like. In one embodiment, the needles 80 may comprisestainless steel. In one embodiment, each needle 80 may comprise aproximal end 82 that is coupled to an associated pocket 64, as shown inFIGS. 3-5. The proximal end 82 of each needle 80 may be coupled to anassociated pocket 64 using a suitable technique including, but notlimited to, mechanical or adhesion techniques.

Each needle 80 preferably comprises a distally-oriented taper 83, whichtransitions into a narrower distal end 84 that is configured to piercethrough tissue, as shown in FIGS. 3-5. The distal end 84 furthercomprises a relatively narrow opening 85. A hollow interior space 86 ofthe needle 80 permits fluid communication between the pocket 64 and theopening 85 of the needle 80, as explained further in FIGS. 3-5 below.

The relatively narrow opening 85 of each needle 80 preferably is sizedto permit dispersal of a therapeutic agent when a predetermined pressurethreshold is exceeded, i.e., the therapeutic agent preferably must beforced through the relatively narrow opening 85. The predeterminedpressure threshold to disperse the therapeutic agent may be exceededwhen a sufficient amount of the therapeutic agent has been injected intothe confines of each pocket 64, i.e., the pocket 64 reaches maximumexpansion from injection of the therapeutic agent, and any additionaltherapeutic agent injected is forced to flow through the opening 85. Inaddition, or as an alternative, inflation of the inner balloon member 50may provide a radially outward force sufficient to urge the therapeuticagent in an outward direction from the pocket 64 through the needle 80,as explained in greater detail below.

As shown in FIG. 2, the apparatus 20 may be used to achieve a biologicaleffect by deploying the needles 80 into engagement with target tissue T.In a first step, a wire guide may be advanced distally towards a targetsite in a vessel or duct. The apparatus 20 then may be advanced over thewire guide in a contracted delivery configuration to the target site viaa wire guide lumen, which may be disposed through the inner cannula 30,i.e., extending adjacent to the inflation lumen 32 and through thedistal end 34 of the inner cannula 30.

In the delivery configuration, the inner balloon member 50 isuninflated. An outer sheath may cover the entire apparatus 20 duringdelivery towards the target tissue T to reduce the likelihood of theneedles 80 inadvertently piercing tissue. The apparatus 20, and inparticular the needles 80, then may be aligned at a desired location,optionally with the assistance of the radiopaque markers 72 and 74. Uponproper alignment, the outer sheath may be retracted to expose the outerballoon member 60 and the needles 80.

In one exemplary technique, an inflation fluid, such as saline, is thendelivered through the inflation lumen 32, through the one or more ports54, and into the interior space 57 of the inner balloon member 50.Inflation of the inner balloon member 50 may cause the needles 80 topierce into the target tissue T, as depicted in FIG. 2. At this time, atherapeutic agent 77 may be delivered through the delivery channel 42and towards the pockets 64 on the outer balloon member 60, as shown inFIG. 2. As the therapeutic agent 77 is delivered, it may fill thepockets 64. Once a sufficient amount of the therapeutic agent 77 hasbeen injected into the confines of each pocket 64, the predeterminedpressure threshold noted above may be exceeded to disperse thetherapeutic agent 77 through the opening 85 of each needle 80 and intothe target tissue T, as depicted in FIG. 2.

In another technique, at least a portion of the therapeutic agent 77 maybe delivered through the delivery channel 42 prior to complete inflationof the inner balloon member 50. In this exemplary technique, the innerballoon member 50 may be uninflated or partially inflated, and thetherapeutic agent 77 may be delivered through the delivery channel 42 tocollect into the pockets 64, without a force sufficient to entirelydisperse the therapeutic agent 77 through the needles 80. Subsequently,further expansion of the inner balloon member 50 to a fully expandedstate may facilitate the dispersal of the therapeutic agent 77 throughthe openings 85 of the needles 80 by applying a radially-outwardpressure upon the pocket 64 and the therapeutic agent 77 disposedtherein.

Upon completion of the procedure using either of the above-referencedtechniques, the inner balloon member 50 may be deflated, and the outersheath may be advanced distally to cover the needles 80. The apparatus20 then may be proximally retracted and removed from the patient's body.

Advantageously, the apparatus and methods described above permitlocalized delivery of a therapeutic agent to treat a medical condition,such as a stenosis or an aneurysm. Further, when used to treatconditions such as stenoses, a two-pronged treatment approach isprovided whereby the inflation of the inner balloon member 50 mayfacilitate dilation of the stenosis while therapeutic agents are locallydelivered to the stenosis through the needles 80.

The therapeutic agents used in conjunction with the apparatus 20, andany of the other apparatuses described below, may be chosen to perform adesired function upon ejection from the needles 80, and may be tailoredfor use based on the particular medical application. For example, thetherapeutic agent can be selected to treat indications such as coronaryartery angioplasty, renal artery angioplasty, carotid artery surgery,renal dialysis fistulae stenosis, or vascular graft stenosis. Thetherapeutic agent may be delivered in any suitable manner and in anysuitable medium. The therapeutic agent may be selected to perform one ormore desired biological functions, for example, promoting the ingrowthof tissue from the interior wall of a body vessel, or alternatively, tomitigate or prevent undesired conditions in the vessel wall, such asrestenosis. Many other types of therapeutic agents may be used inconjunction with the apparatus 20.

The therapeutic agent employed also may comprise an antithrombogenicbioactive agent, e.g., any bioactive agent that inhibits or preventsthrombus formation within a body vessel. Types of antithromboticbioactive agents include anticoagulants, antiplatelets, andfibrinolytics. Anticoagulants are bioactive materials which act on anyof the factors, cofactors, activated factors, or activated cofactors inthe biochemical cascade and inhibit the synthesis of fibrin.Antiplatelet bioactive agents inhibit the adhesion, activation, andaggregation of platelets, which are key components of thrombi and playan important role in thrombosis. Fibrinolytic bioactive agents enhancethe fibrinolytic cascade or otherwise aid in dissolution of a thrombus.Examples of antithrombotics include but are not limited toanticoagulants such as thrombin, Factor Xa, Factor VIIa and tissuefactor inhibitors; antiplatelets such as glycoprotein IIb/IIIa,thromboxane A2, ADP-induced glycoprotein IIb/IIIa, and phosphodiesteraseinhibitors; and fibrinolytics such as plasminogen activators, thrombinactivatable fibrinolysis inhibitor (TAFI) inhibitors, and other enzymeswhich cleave fibrin.

Additionally, or alternatively, the therapeutic agents may includethrombolytic agents used to dissolve blood clots that may adverselyaffect blood flow in body vessels. A thrombolytic agent is anytherapeutic agent that either digests fibrin fibres directly oractivates the natural mechanisms for doing so. Examples of commercialthrombolytics, with the corresponding active agent in parenthesis,include, but are not limited to, Abbokinase (urokinase), AbbokinaseOpen-Cath (urokinase), Activase (alteplase, recombinant), Eminase(anitstreplase), Retavase (reteplase, recombinant), and Streptase(streptokinase). Other commonly used names are anisoylatedplasminogen-streptokinase activator complex; APSAC; tissue-typeplasminogen activator (recombinant); t-PA; rt-PA. While a few exemplarytherapeutic agents have been listed, it will be apparent that numerousother suitable therapeutic agents may be used in conjunction with theapparatus 20 and delivered through the plurality of needles 80 toperform various biological functions.

Referring to FIGS. 3-5, further features of an exemplary pocket 64 andan associated needle 80 are shown. Each of the plurality of pockets 64may comprise a delivery configuration and an injection configuration. InFIG. 3, the delivery configuration of the pocket 64 and associatedneedle 80 is shown. The pocket 64 comprises a recess 65 for receiving atleast a portion of and preferably the whole of the needle 80.Preferably, the recess 65 is disposed substantially near the center ofthe pocket 64. The recess 65 may comprise a taper 66, which allows anouter portion of the pocket 64 to be disposed relatively further awayfrom the distal end 84 of the needle 80, as shown in FIG. 3. If thedistal end 84 of the needle 80 becomes off-center, then the taper 83 ofthe needle 80 will substantially cooperate with the taper 66 of thepocket 64. Preferably, the distal end 84 of the needle 80 will bedisposed just distal to the pocket 64 at all times (to be within theperimeter of the pocket 64) to reduce or eliminate inadvertent piercingof the pocket 64. Moreover, since the needle 80 may be disposedsubstantially within the recess 65 of the pocket 64 during delivery, aprotective outer sheath may be longitudinally advanced over the needle80.

In FIG. 4, expansion of the inner balloon member 50 applies a radiallyoutward pressure upon the pocket 64, thereby causing at least partialeversion of the recess 65 and further radial projection of the needle80. At this time, the distal end 80 of the needle may pierce the targettissue T. In FIG. 5, further expansion of the inner balloon member 50 toa fully expanded state may facilitate the dispersal of the therapeuticagent 77 through the opening 85 of the needle 80 by applying additionalpressure upon the pocket 64 and the therapeutic agent 77 in a radiallyoutward direction.

Referring now to FIGS. 6-7, another embodiment of apparatus 120 fordelivering one or more therapeutic agents comprises a catheter 130having a plurality of discrete pockets 164. The discrete pockets 164 aresimilar to the pockets 64 of FIGS. 1-2. However, in this example, asingle balloon member 150 may be used, and each discrete pocket 164 maybe coupled directly to an exterior surface 156 of the balloon member150, or formed integrally with the balloon, without being placed influid communication with other pockets 164.

The discrete pockets 164 may be affixed to the exterior surface 156 ofthe balloon member 150 via adhesive or other suitable means. Atherapeutic agent is held in each discrete pocket 164, and a needle 180is associated with each discrete pocket 164, as shown in FIGS. 6-7. Theneedles 180 preferably are similar to the needles 80 of FIGS. 3-5, andpreferably are deployed in a similar manner.

The therapeutic agent held within each pocket 164 may be dispersedthrough the distal opening of each needle 180 upon inflation of theballoon member 150. More specifically, inflation of the balloon member150 imposes a radially-outward pressure upon the pockets 164 and thetherapeutic agent sufficient to disperse the therapeutic agent throughthe needles 180.

In the embodiment of FIGS. 6-7, various pockets 164 a-164 c may compriseassociated needles 180 a-180 c having different lengths L, as measuredfrom the proximal tip to the distal tip of the needle. In theillustrative example, each needle 180 c comprises a first length, whichis larger than a second length of each needle 180 b, which in turn islarger than a third length of each needle 180 a, as depicted in FIGS.6-7.

Advantageously, the different needles 180 a-180 c may pierce tissue T atdifferent depths, i.e., based on the individual lengths L of the needles180 a-180 c. This may help optimize delivery of one or more therapeuticagents to different depths within tissue. For example, the distal end 84of each needle 180 a may be disposed substantially within an intimallayer, the distal end 84 of each needle 180 b may be disposedsubstantially within a medial layer, and the distal end 84 of eachneedle 180 c may be disposed substantially within an adventitial layerof tissue. Accordingly, one or more therapeutic agents may be deliveredto multiple layers of tissue upon deployment of the balloon member 150.

As another advantage, the provision of multiple discrete pockets 164a-164 c having needles 180 a-180 c of different lengths may permit theinjection of different therapeutic agents to different tissue regions.For example, a first therapeutic agent may be disposed in each pocket164 a, while second and third therapeutic agents may be disposed in eachpocket 164 b and 164 c, respectively. Upon inflation of the balloonmember 150, the first, second and third therapeutic agents are deliveredthrough their respective needles 180 a-180 c into different layers of apatient's tissue. Accordingly, the use of multiple needles 180 a-180 c,tied to multiple therapeutic agents and tailored for different layers ofthe anatomy, allows numerous injections to be consolidated into a singleprocedure.

For example, in an endovascular application, different cell populationsmay be delivered to different depths of the vessel wall. In one example,fibroblasts (collagen producing cells) may be delivered to the tunicaadventitia, smooth muscle cells (elastin maintenance cells) may bedelivered to the tunica media, and endothelial cells (lumen liningcells) may be delivered to the tunica intima. The balloon member 150also can deliver site-specific appropriate growth factors or solublematrix proteins to the different layers of a vessel wall. Thesetherapeutic agents could assist in the regulation of the cellpopulations in the targeted layers of the vessel wall or assist in theacute stabilization of the extracellular matrix.

In one example, where the device is used to deliver a therapeutic agentinto an aortic or peripheral artery, an individual lengths L of theneedle 180 a may be about 0.1 to 1.0 mm in length with an orificediameter of about 50 to 1000 pm to deliver a therapeutic agent or cellsto the tunica intima. An individual lengths L of the needle 180 b may beabout 1.0 to 3.5 mm in length with an orifice diameter of about 50 to1000 μm to deliver a therapeutic agent or cells to the tunica media, andan individual lengths L of the needle 180 c may be about 3.5 to 5.0 mmin length with an orifice diameter of about 50 to 1000 μm to deliver atherapeutic agent or cells to the tunica adventitia. If there isthrombus formation along an inner wall of the vessel, then the needlelength may be dimensioned to account for the estimated thickness of thethrombus, in addition to the dimensions stated above. It should be notedthat such dimensions are provided for exemplary purposes only and arenot intended to be limiting.

As a further example, the apparatus 120 may be used for intra-urethralor intra-rectal injections of cells into the sphincter of eitherlocation at multiple depths simultaneously. This would permit a singleprocedure and injection that would deliver cells to multiple depths ofthe tissue, thereby providing increased exposure of the entire sphincterto the new cell population.

Still further applications of the apparatus 120 are possible. Moreover,it will be appreciated the while three different needles lengths havebeen discussed, greater or fewer needle lengths may be provided.Further, greater or fewer than three therapeutic agents may be provided,and multiple different therapeutic agents may be delivered into the samelayer of tissue.

Referring now to FIGS. 8-10, another embodiment is disclosed fordelivering at least one therapeutic agent. Like the embodiment of FIGS.6-7, apparatus 220 comprises needles 280 a-280 c having differentlengths, which may be used to deliver one or more therapeutic agents todifferent layers of tissue. One main difference regarding FIGS. 8-10 isthat a first series of pockets 264 a are in fluid communication with oneanother to deliver a first therapeutic agent, a second series of pockets264 b are in fluid communication with one another to deliver a secondtherapeutic agent, and a third series of pockets 264 are in fluidcommunication with one another to deliver a third therapeutic agent.

In FIG. 8, the apparatus 220 comprises a catheter 230 having proximaland distal regions and a balloon member 250 coupled to the distal regionof the catheter 230. The catheter 230 may comprise an inflation lumen232 and first, second and third delivery channels 242 a-242 c,respectively, as shown in FIG. 9. The inflation lumen 232 and thedelivery channels 242 a-242 c may be integrally formed with the catheter230, e.g., by extrusion. Alternatively, separate inflation and deliverychannels may be provided using one or more additional pieces of tubingdisposed on an external surface of the catheter 230.

The first series of pockets 264 a may be placed in fluid communicationwith each other, and with the first delivery channel 242 a of thecatheter 230, via a series of balloon channels 262 a, as shown in FIG.8. The balloon channels 262 a may be formed by attaching a thin layer ofballoon material, or another suitable material, over the main balloonmember 250. Lateral edges of the balloon channels 262 a then may beadhered to the outer surface of the balloon member 250, while a centralchannel of the balloon channel 262 a is not adhered to the balloonmember 250 to provide a pathway for fluid flow on the outside of theballoon member 250. In a similar manner, a series of balloon channels262 b may be used to provide fluid communication between the secondseries of pockets 264 b and the second delivery channel 242 b, while aseries of balloon channels 262 c may be used to provide fluidcommunication between the third series of pockets 264 c and the thirddelivery channel 242 c, as shown in FIG. 8.

A proximal region of the catheter 230 may be coupled to a proximalassembly 270 via a coupling member 276, as shown in FIG. 10. Theproximal assembly 270 may comprise a first port 271, which is in fluidcommunication with the inflation lumen 232, and additional ports 272a-272 c, which are in fluid communication with the delivery channels 242a-242 c, respectively. A coupling member 277 may be disposed between themain body of the catheter 230 and the balloon member 250 to facilitatedirection of flow from the delivery channels 242 a-242 c into theirrespective balloon channels 262 a-262 c.

In use, after the needles 280 a-280 c have been advanced and positionedadjacent to a target site, the balloon member 250 may be inflated byproviding an inflation fluid, such as saline, through the first port 271and the inflation lumen 232. Upon inflation of the balloon member 250,the needles 280 a-280 c may engage tissue. Since the needles 280 a-280 ccomprise different lengths, as described above, they may extend intodifferent depths of the tissue at the target site.

A first therapeutic agent then may be delivered through the port 272 a,through the delivery channel 242 a and the balloon channels 262 a andinto the associated pockets 264 a, then dispersed through the associatedneedles 280 a to a first depth in the tissue. Similarly, a secondtherapeutic agent then may be delivered through the port 272 b, throughthe delivery channel 242 b and the balloon channels 262 b, and into theassociated pockets 264 b, then dispersed through the associated needles280 b to a second depth in the tissue. Finally, a third therapeuticagent then may be delivered through the port 272 c, through the deliverychannel 242 c and the balloon channels 262 c, and into the associatedpockets 264 c, then dispersed through the associated needles 280 c to athird depth in the tissue.

Optionally, the balloon member 250 then may be deflated, a sheath may beadvanced to cover the needles 280 a-280 c, and the catheter 230 may berotated circumferentially, e.g., 90 or 180 degrees, to align thedifferent needles with different circumferential sections of the tissue.The sheath then may be retracted, the balloon member 250 re-inflated,and the therapeutic agents then are delivered to a new region within thetissue.

Referring to FIG. 11, the balloon channels 262 a-262 c, the pockets 264a-264 c and the needles 280 a-280 c are arranged in a slightly differentmanner than shown in FIGS. 8-10. In FIG. 11, the balloon channels 262a-262 c, the pockets 264 a-264 c and the needles 280 a-280 c aredisposed in substantially closer proximity around the perimeter of theballoon member 250. In this example, substantially hexagonal shapedpockets 264 a-264 c are provided. The pockets 264 a of a first row areoffset with the pockets 264 b of an adjacent row, which in turn areoffset from the pockets 264 c of a third row, thereby allowing adjacentballoon channels 262 a-262 c and pockets 264 a-264 c to be nestledtogether, as shown in FIG. 11.

In the embodiment of FIG. 11, first, second and third therapeutic agentsmay be delivered through the needles 280 a-280 c, respectively. Thedifferent therapeutic agents are injected at nearly the same tissuelocation, since the pockets 264 a-264 c and associated needles 280 a-280c are nestled together, but the different therapeutic agents may beinjected at different tissue depths since the different needles 280a-280 c may comprise different lengths, as noted above. After injectionof the different therapeutic agents to different depths in the tissue,the balloon member 250 may be deflated, a sheath may be advanced tocover the needles 280 a-280 c, and the catheter may be rotatedcircumferentially, e.g., 90 or 180 degrees, to align the needles 280a-280 c with different circumferential sections of the tissue. Thesheath then may be retracted, the balloon re-inflated, and thetherapeutic agents then are delivered to a new region within the tissue.

Referring now to FIGS. 12-13, in some embodiments, a balloon membercomprises a central lumen configured to allow uninterrupted blood flowduring the delivery of one or more therapeutic agents according to thetechniques described above. In FIG. 12, apparatus 320 comprises acatheter 330 having an inflation lumen 332, and further comprises atoroidally-shaped balloon member 350 having a first end 352, a secondend 353, an inner surface 355 and an outer surface 356. In the inflatedstate of FIG. 12, a central lumen 354 is formed within the inner surface355 and between the first and seconds ends 352 and 353.

A plurality of discrete pockets 364 having associated needles 380 aredisposed on the outer surface 356 of the balloon member 350, andpreferably are provided in accordance with the discrete pockets 164a-164 c and the needles 180 a-180 c of FIGS. 6-7 above. When the balloonmember 350 is inflated via the inflation lumen 332, the needles 380 maypenetrate into tissue a predetermined depth and dispense one or moretherapeutic agents, as set forth in FIGS. 6-7 above. Moreover, thecentral lumen 354 permits blood flow within the vessel or duct while theballoon member 350 is inflated and the therapeutic agents are dispensed.

In FIG. 13, apparatus 420 comprises an inner cannula 430 having aninflation lumen 432 and an outer cannula 440 forming a delivery channel442 therein. The inner and outer cannulas 430 and 440 may be providedgenerally in accordance with the inner and outer cannulas 30 and 40,respectively, as described in FIG. 1 above. The apparatus 420 furthercomprises a toroidally-shaped inner balloon member 450, which is similarto the balloon member 350 of FIG. 12. The inner balloon member 450comprises a first end 452, a second end 453, an inner surface 455 and anouter surface 456. In an inflated state, a central lumen 454 is formedwithin the inner surface 455 and between the first and seconds ends 452and 453, as depicted in FIG. 13.

A plurality of interconnected pockets 464 having associated needles 480are disposed on an outer balloon member 460, which preferably is similarto the outer balloon member 60 of FIG. 1. In use, the inner balloonmember 450 is inflated via the inflation lumen 432, and then atherapeutic agent may be delivered through the channel 442, the pockets464 and the associated needles 480, thereby dispensing the therapeuticagent into the tissue as set forth above. Moreover, the central lumen454 permits blood flow within the vessel or duct while the balloonmember 450 is inflated and the therapeutic agents are dispensed.

While various embodiments of the invention have been described, it willbe apparent to those of ordinary skill in the art that many moreembodiments and implementations are possible within the scope of theinvention. In this regard, the various features of the describedembodiments can be incorporated into the other described embodiments,singly or in combination. Moreover, the advantages described herein arenot necessarily the only advantages of the invention and it is notnecessarily expected that every embodiment of the invention will achieveall of the advantages described.

The disclosures in U.S. patent application No. 61/091,894, from whichthis application claims priority, and in the abstract accompanying thisapplication are incorporated herein by reference.

The invention claimed is:
 1. An apparatus for treating tissue at atarget site, the apparatus comprising: an inner cannula having proximaland distal regions and an inflation lumen disposed therein; an outercannula having proximal and distal regions, wherein the outer cannula isdisposed substantially co-axially over the inner cannula to form adelivery channel therebetween; an inner balloon member disposed on thedistal region of the inner cannula, the inner balloon member havinguninflated and inflated states; an outer balloon member disposedsubstantially over the inner balloon member; a plurality of pockets on asurface of the outer balloon member; and a plurality of needles, whereat least one needle is associated with at least one of the plurality ofpockets, where the inflation lumen is sized to receive an inflationfluid to inflate the inner balloon member and cause the plurality ofneedles to engage tissue, where each of the plurality of needlescomprise openings sized to disperse a therapeutic agent, received viathe delivery channel and the plurality of pockets, into the tissue, andwhere each of the plurality of pockets comprise a bulbous shape formedintegrally into the outer balloon member.
 2. The apparatus of claim 1where each of the plurality of pockets comprises a deliveryconfiguration having a recess for receiving a portion of an associatedneedle, and further comprises an injection configuration whereby therecess is at least partially everted and the associated needle projectsradially outward.
 3. The apparatus of claim 1 where a proximal end ofthe outer balloon member is affixed to the outer cannula and a distalend of the outer balloon is affixed to the inner cannula.
 4. Theapparatus of claim 1 where the inner balloon member comprises a centrallumen configured to permit blood flow therethrough when the innerballoon member is in the inflated state.
 5. The apparatus of claim 1where a first needle of the plurality of needles comprises a firstlength that is greater than a second length of a second needle of theplurality of needles.
 6. An apparatus for treating tissue at a targetsite, the apparatus comprising: an inner cannula having proximal anddistal regions and an inflation lumen disposed therein; an outer cannulahaving proximal and distal regions, wherein the outer cannula isdisposed substantially co-axially over the inner cannula to form adelivery channel therebetween; an inner balloon member disposed on thedistal region of the inner cannula, the inner balloon member havinguninflated and inflated states; an outer balloon member disposedsubstantially over the inner balloon member; a plurality of pockets on asurface of the outer balloon member; and a plurality of needles, whereat least one needle is associated with at least one of the plurality ofpockets, where the inflation lumen is sized to receive an inflationfluid to inflate the inner balloon member and cause the plurality ofneedles to engage tissue, where each of the plurality of needlescomprise openings sized to disperse a therapeutic agent, received viathe delivery channel and the plurality of pockets, into the tissue, andwhere each of the plurality of pockets comprises a deliveryconfiguration having a recess for receiving a portion of an associatedneedle, and further comprises an injection configuration whereby therecess is at least partially everted and the associated needle projectsradially outward.
 7. The apparatus of claim 6 where each of theplurality of pockets comprise a bulbous shape formed integrally into theouter balloon member.
 8. The apparatus of claim 6 where a proximal endof the outer balloon member is affixed to the outer cannula and a distalend of the outer balloon is affixed to the inner cannula.
 9. Theapparatus of claim 6 where the inner balloon member comprises a centrallumen configured to permit blood flow therethrough when the innerballoon member is in the inflated state.
 10. The apparatus of claim 6where a first needle of the plurality of needles comprises a firstlength that is greater than a second length of a second needle of theplurality of needles.
 11. An apparatus for treating tissue at a targetsite, the apparatus comprising: an inner cannula having proximal anddistal regions and an inflation lumen disposed therein; an outer cannulahaving proximal and distal regions, wherein the outer cannula isdisposed substantially co-axially over the inner cannula to form adelivery channel therebetween; an inner balloon member disposed on thedistal region of the inner cannula, the inner balloon member havinguninflated and inflated states; an outer balloon member disposedsubstantially over the inner balloon member; a plurality of pockets on asurface of the outer balloon member; and a plurality of needles, whereat least one needle is associated with at least one of the plurality ofpockets, where the inflation lumen is sized to receive an inflationfluid to inflate the inner balloon member and cause the plurality ofneedles to engage tissue, where each of the plurality of needlescomprise openings sized to disperse a therapeutic agent, received viathe delivery channel and the plurality of pockets, into the tissue, andwhere a proximal end of the outer balloon member is affixed to the outercannula and a distal end of the outer balloon is affixed to the innercannula.
 12. The apparatus of claim 11 where each of the plurality ofpockets comprise a bulbous shape formed integrally into the outerballoon member.
 13. The apparatus of claim 11 where each of theplurality of pockets comprises a delivery configuration having a recessfor receiving a portion of an associated needle, and further comprisesan injection configuration whereby the recess is at least partiallyeverted and the associated needle projects radially outward.
 14. Theapparatus of claim 11 where the inner balloon member comprises a centrallumen configured to permit blood flow therethrough when the innerballoon member is in the inflated state.
 15. The apparatus of claim 11where a first needle of the plurality of needles comprises a firstlength that is greater than a second length of a second needle of theplurality of needles.
 16. An apparatus for treating tissue at a targetsite, the apparatus comprising: an inner cannula having proximal anddistal regions and an inflation lumen disposed therein; an outer cannulahaving proximal and distal regions, wherein the outer cannula isdisposed substantially co-axially over the inner cannula to form adelivery channel therebetween; an inner balloon member disposed on thedistal region of the inner cannula, the inner balloon member havinguninflated and inflated states; an outer balloon member disposedsubstantially over the inner balloon member; a plurality of pockets on asurface of the outer balloon member; and a plurality of needles, whereat least one needle is associated with at least one of the plurality ofpockets, where the inflation lumen is sized to receive an inflationfluid to inflate the inner balloon member and cause the plurality ofneedles to engage tissue, where each of the plurality of needlescomprise openings sized to disperse a therapeutic agent, received viathe delivery channel and the plurality of pockets, into the tissue, andwhere a first needle of the plurality of needles comprises a firstlength that is greater than a second length of a second needle of theplurality of needles.
 17. The apparatus of claim 16 where each of theplurality of pockets comprise a bulbous shape formed integrally into theouter balloon member.
 18. The apparatus of claim 16 where each of theplurality of pockets comprises a delivery configuration having a recessfor receiving a portion of an associated needle, and further comprisesan injection configuration whereby the recess is at least partiallyeverted and the associated needle projects radially outward.
 19. Theapparatus of claim 16 where a proximal end of the outer balloon memberis affixed to the outer cannula and a distal end of the outer balloon isaffixed to the inner cannula.
 20. The apparatus of claim 16 where theinner balloon member comprises a central lumen configured to permitblood flow therethrough when the inner balloon member is in the inflatedstate.